| 1. |
- Axelsen, Mette, 1965, et al.
(författare)
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Suppression of nocturnal fatty acid concentrations by bedtime carbohydrate supplement in type 2 diabetes: effects on insulin sensitivity, lipids, and glycemic control.
- 2000
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Ingår i: The American journal of clinical nutrition. - 0002-9165. ; 71:5, s. 1108-14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bedtime ingestion of slow-release carbohydrates leads to sustained nocturnal fatty acid suppression and improved glucose tolerance in type 2 diabetic patients. OBJECTIVE: This study assessed the effects of 2 different doses of bedtime carbohydrate supplement (BCS) on morning glycemic control and glycated hemoglobin (Hb A(1c)) in type 2 diabetic patients. In addition, the effects of the high-dose BCS on insulin sensitivity and postprandial glucose and triacylglycerol concentrations were assessed. DESIGN: Two BCS doses were studied separately in 7-wk randomized, placebo-controlled, double-blind studies with either a parallel (low-dose BCS; n = 24 patients) or crossover (high-dose BCS; n = 14 patients) design. The effects of the low and high doses (0.30 and 0.55 g uncooked cornstarch/kg body wt, respectively) were compared with those of a starch-free placebo. RESULTS: Compared with the starch-free placebo, the high-dose BCS ( approximately 45 g) produced enhanced nocturnal glucose (P < 0.01) and insulin (P < 0.01) concentrations as well as a 32% suppression of fatty acid concentrations (P < 0.01). Moreover, glucose tolerance (P < 0.05) and C-peptide response (P < 0.05) improved after breakfast the next morning. The low-dose BCS ( approximately 25 g) improved fasting blood glucose concentrations (P < 0.05). However, there were no improvements in insulin sensitivity, postprandial triacylglycerol concentrations, or Hb A(1c) after 7 wk. CONCLUSION: Nocturnal fatty acid suppression by BCS improved fasting and postprandial blood glucose concentrations in type 2 diabetic patients the next morning. In contrast, no improvements in insulin sensitivity, postprandial triacylglycerol concentrations, or long-term glycemic control assessed by Hb A(1c) were seen after BCS supplementation.
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| 2. |
- Axelsson, T., et al.
(författare)
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Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects
- 2001
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Ingår i: J Intern Med. - 0954-6820. ; 249:6, s. 539-44
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to examine if an acute nicotine infusion alters insulin sensitivity to a similar degree in type 2 diabetic patients as in healthy control subjects. DESIGN: . Double-blind, cross-over, placebo-controlled, randomized experimental study. Nicotine 0.3 microg kg-1 min(-1) or NaCl was infused (2 h) during a euglycaemic hyperinsulinaemic clamp (4 h) to assess insulin sensitivity. SETTING: University research laboratory. SUBJECTS: Six male and female type 2 diabetic patients [DM2; age 54 +/- 10 (mean +/- SD) years; body mass index (BMI) 25.6 +/- 2.9 kg m(-2)] treated with diet or one oral hypoglycaemic agent and six age- and BMI-matched control subjects (Ctr). MAIN OUTCOME MEASURE: Insulin sensitivity (rate of glucose infusion per kg fat free body mass and minute), nicotine and free fatty acid (FFA) levels, pulse rate and blood pressure. RESULTS: The infusions produced similar nicotine levels in both groups. In the absence of nicotine, DM2 were more insulin resistant than Ctr (6.7 +/- 0.4 vs. 10.9 +/- 0.3 mg kg-1 LBM min(-1), respectively; P < 0.0001). This insulin resistance was further aggravated by the nicotine infusion in DM2 but not in Ctr (4.6 +/- 0.3 vs. 10.9 +/- 0.3 mg kg(-1) LBM min(-1); P < 0.0001). Only minor differences were seen in FFA levels, pulse rates and blood pressure. CONCLUSIONS: At this low infusion rate, nicotine aggravated the insulin resistance in DM2 but not in Ctr. This finding may be because of the (dysmetabolic) diabetic state per se or to an increased sensitivity to environmental factors associated with a genetic predisposition for type 2 diabetes. These results show that diabetic subjects are particularly susceptible to the detrimental effects of nicotine.
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| 3. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Predictors of weight loss in adults with topiramate-treated epilepsy.
- 2003
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Ingår i: Obesity research. - 1071-7323. ; 11:4, s. 556-62
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We examined predictors of weight loss with topiramate, an anticonvulsant associated with weight loss in adults. RESEARCH METHODS AND PROCEDURES: In this uncontrolled, prospective clinical trial, topiramate was added to existing anticonvulsants in adults (40 to 110 kg) with partial-onset seizures. Primary measurements were change from baseline weight after 3 months and 1 year in patients completing 1 year of topiramate treatment (N = 38). Physiological and metabolic measures were analyzed for correlation with weight loss during topiramate treatment. RESULTS: In patients who completed 1 year of topiramate treatment, baseline weight was reduced in 82% at 3 months and in 86% at 1 year. Mean body weight was reduced 3.0 kg (3.9% of baseline) at 3 months and 5.9 kg (7.3%) at 1 year. In obese patients [body mass index (BMI) >/= 30 kg/m(2)], mean weight loss was 4.2 kg (4.3%) at 3 months and 10.9 kg (11.0%) at 1 year. Weight loss was primarily caused by reduction in body fat mass. For all patients, weight loss at 3 months correlated most strongly with reduced caloric intake (p = 0.02). At 1 year, caloric intake had returned to baseline levels; weight loss correlated most strongly with higher baseline BMI (p = 0.0007). DISCUSSION: Our results suggest that weight loss occurs in most adults treated with topiramate and is sustained for at least 1 year. Reduced caloric intake may account, in part, for weight loss during early treatment. The pattern of weight loss differs according to baseline BMI, with obese patients experiencing greater weight loss during continued therapy.
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| 4. |
- Carvalho, Eugénia, 1967, et al.
(författare)
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Impaired phosphorylation and insulin-stimulated translocation to the plasma membrane of protein kinase B/Akt in adipocytes from Type II diabetic subjects
- 2000
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Ingår i: Diabetologia. - 0012-186X. ; 43:9, s. 1107-15
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: To examine protein kinase B/Akt distribution and phosphorylation in response to insulin in different subcellular fractions of human fat cells from healthy subjects and subjects with Type II (non-insulin-dependent) diabetes mellitus. METHODS: We prepared subcellular fractions of plasma membranes (PM), low density microsomes and cytosol and examined gene and protein expression as well as serine and threonine phosphorylation in response to insulin. RESULTS: Protein kinase B/Akt mRNA as well as total protein kinase B/Akt protein in whole-cell lysate and cytosol were similar in both groups. Insulin increased protein kinase B/Akt translocation to the the plasma membrane about twofold [(p < 0.03) in non-diabetic cells but this effect was impaired in diabetic cells (approximately 30%; p > 0.1)]. In both groups, protein kinase B/Akt threonine phosphorylation considerably increased in low density microsomes and cytosol whereas serine phosphorylation was predominant in the plasma membrane. Phosphatidylinositol-dependent kinase 1, which partially activates and phosphorylates protein kinase B/Akt on the specific threonine site, was predominant in cytosol but it was also recovered in low density microsomes. Serine phosphorylation in response to insulin was considerably reduced (50-70 %; p < 0.05) in diabetic cells but threonine phosphorylation was less reduced (approximately 20%). Wortmannin inhibited these effects of insulin supporting a role for PI3-kinase activation. CONCLUSION/INTERPRETATION: Insulin stimulates a differential subcellular pattern of phosphorylation of protein kinase B/Akt. Furthermore, insulin-stimulated translocation of protein kinase B/Akt to the plasma membrane, where serine phosphorylation and full activation occurs, is impaired in Type II diabetes. Threonine phosphorylation was much less reduced. This discrepancy may be related to differential activation of phosphatidylinositol 3-kinase in the different subcellular compartments and phosphatidylinositol-dependent kinase 1 having high affinity for phosphatidylinositol phosphate 3.
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| 5. |
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| 6. |
- Hellebö Johanson, Else, 1969, et al.
(författare)
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Early alterations in the postprandial VLDL1 apoB-100 and apoB-48 metabolism in men with strong heredity for type 2 diabetes
- 2004
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Ingår i: J Intern Med. - 0954-6820. ; 255:2, s. 273-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the postprandial triglyceride-rich lipoprotein (TRL) metabolism, specifically the concentrations of very low-density lipoproteins (VLDL); from intestine (apoB-48) and liver (apoB-100), in men with normal fasting triglycerides but at increased risk of developing type 2 diabetes. DESIGN: Cross-sectional study. SUBJECTS AND SETTINGS: Sixteen healthy men with at least two first-degree relatives with type 2 diabetes were individually matched with 16 control subjects without known diabetes heredity for: age, body mass index, and fasting triglyceride level. They underwent an 8-h meal tolerance test (919 kcal, 51 g fat) during which lipoproteins were separated by density gradient ultracentrifugation. They were characterized by euglycaemic hyperinsulinaemic clamp, peak VO2, 7-day diet registration and computed tomography. RESULTS: The relatives were, as expected, more insulin resistant than the controls and had increased concentration of postprandial VLDL1 particles (49% higher for VLDL1 apoB-48, P = 0.04 and 21% higher for VLDL1 apoB-100, P = 0.048). The elevation was related to insulin sensitivity, but not to lifestyle and body composition. Moreover, the concentration of postprandial triglycerides in VLDL1 fraction was inversely related to low-density lipoprotein (LDL) size in both relatives (rs = -0.60, P = 0.03) and controls (rs = -0.72, P = 0.004). There were no differences in the concentration of triglycerides or apoB-48 and apoB-100 particles in the other fractions (plasma, chylomicron or VLDL2). CONCLUSION: Increased postprandial concentration of TRLs in the VLDL1 fraction seems to be present at an early stage in the development of diabetes and probably contributes to the excess risk of future coronary events in insulin-resistant men.
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| 7. |
- Jenkins, D J, et al.
(författare)
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Dietary fibre, lente carbohydrates and the insulin-resistant diseases.
- 2000
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Ingår i: The British journal of nutrition. - 0007-1145. ; 83 Suppl 1
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Forskningsöversikt (refereegranskat)abstract
- Several epidemiological studies link consumption of fibre-rich foods to a reduced risk of type 2 diabetes and CHD. The 'fibre hypothesis' suggested that this was a direct effect of fibre. However, fibre-rich foods contain different types of fibre as well as other potentially beneficial compounds, and many foods naturally high in fibre have low glycaemic and insulinaemic indices, possibly due to food form. The question therefore emerges as to the effect of isolated fibre per se on insulin sensitivity, lipids and other risk factors associated with the metabolic syndrome. Many beneficial effects are seen with pharmacological doses of isolated viscous soluble fibre, including improved insulin sensitivity, decreased LDL-cholesterol levels and decreased clotting factors. Similar effects are seen with low glycaemic-index foods. In contrast, insoluble non-viscous cereal fibre is not seen to act directly on risk factors when taken in refined foods such as in milled flour. Since cereal fibre, the major type of fibre in western diets, does not directly act on the risk factors for the metabolic syndrome, the question remains as to possible mechanisms. Until now, fibre and the nature and processing of the starch and particle size have been seen as the main determinants of the metabolic response to starchy foods. However, fibre-rich foods also have an increased protein-to-carbohydrate ratio. Hence we suggest that the protective effect of fibre may also be due to increased vegetable protein content, which may act directly to reduce clotting factors and oxidized LDL-cholesterol levels.
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| 8. |
- Johanson, Else H, et al.
(författare)
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Fat distribution, lipid accumulation in the liver, and exercise capacity do not explain the insulin resistance in healthy males with a family history for type 2 diabetes.
- 2003
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 88:9, s. 4232-8
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Tidskriftsartikel (refereegranskat)abstract
- To explore the mechanisms for the insulin resistance associated with a family history of type 2 diabetes, we studied 16 healthy men with at least two first-degree relatives with type 2 diabetes and 16 control subjects without known heredity. They were pair-wise matched for age, body mass index, and fasting triglycerides and underwent an oral glucose tolerance test, iv glucose infusion to measure the early insulin secretion, euglycemic hyperinsulinemic clamp, computed tomography scan, 7-d food record, and a cardiopulmonary exercise test to measure peak oxygen uptake. Insulin sensitivity index was 30% lower (P = 0.02) in relatives, compared with controls, but fasting and 2-h blood glucose and first-phase insulin secretion were similar. There were no differences in mean fasting free fatty acid levels, amount of sc or visceral adipose tissue, or fat accumulation in the liver. Dietary intake and peak oxygen uptake were also similar. However, multiple regression analysis of both groups showed that fat in the liver and physical capacity were, like known heredity for type 2 diabetes, independent predictors of insulin sensitivity. Thus, lipid accumulation in the liver and physical capacity are related to insulin sensitivity, but neither of these factors nor the amount and distribution of the body fat can explain the insulin resistance associated with a family history for type 2 diabetes.
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| 9. |
- Rotter Sopasakis, Victoria, 1972, et al.
(författare)
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High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator
- 2004
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Ingår i: Obes Res. - 1071-7323. ; 12:3, s. 454-60
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the possibility that interleukin-6 (IL-6) can act as a paracrine regulator in adipose tissue by examining effects on adipogenic genes and measuring interstitial IL-6 concentrations in situ. RESEARCH METHODS AND PROCEDURES: Circulating and interstitial IL-6 concentrations in abdominal and femoral adipose tissue were measured using the calibrated microdialysis technique in 20 healthy male subjects. The effects of adipose cell enlargement on gene expression and IL-6 secretion were examined, as well as the effect of IL-6 in vitro on gene expression of adiponectin and other markers of adipocyte differentiation. RESULTS: The IL-6 concentration in the interstitial fluid was approximately 100-fold higher than that in plasma, suggesting that IL-6 may be a paracrine regulator of adipose tissue. This was further supported by the finding that adding IL-6 in vitro at similar concentrations down-regulated the expression of adiponectin, aP2, and PPARgamma-2 in cultured human adipose tissue. In addition, gene expression and release of IL-6, both in vivo and in vitro, correlated with adipose cell size. DISCUSSION: These data suggest that IL-6 may be a paracrine regulator of adipose tissue. Furthermore, increased adipose tissue production of IL-6 after hypertrophic enlargement of the adipose cells may detrimentally affect systemic insulin action by inducing adipose tissue dysfunction with impaired differentiation of the pre-adipocytes and/or adipocytes and lower adiponectin.
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| 10. |
- Rotter Sopasakis, Victoria, 1972, et al.
(författare)
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Short-term infusion of interleukin-6 does not induce insulin resistance in vivo or impair insulin signalling in rats
- 2004
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 47:11, s. 1879-87
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Interleukin-6 has been implicated in the insulin resistance associated with obesity and impaired glucose tolerance. Previous studies in vitro have shown that IL-6 rapidly (1-2 h) impairs cellular insulin signalling and action through an increased expression of suppressor of cytokine signalling (SOCS)-3. In the present study, IL-6 or saline was infused in rats that were simultaneously in a state of hyperinsulinaemia. Muscle, liver and adipose tissue were excised after 2 h to examine potential effects on insulin signalling or gene expression. METHODS: The rats were infused with IL-6 or saline during a euglycaemic-hyperinsulinaemic clamp and the glucose infusion rate was measured after 90 to 120 min. Signal transducer and activator of transcription (STAT)3 phosphorylation and insulin-stimulated tyrosine phosphorylation of the insulin receptors and IRS were measured with immunoblotting and gene expression through real-time PCR. RESULTS: No inhibitory effect of IL-6 on insulin-stimulated whole-body glucose uptake was seen in spite of high circulating levels of IL-6 (0.85+/-0.08 nmol/l). Tyrosine phosphorylation of the insulin receptors and IRS was also unchanged in the liver, skeletal muscles and adipose tissue. However, tyrosine phosphorylation of STAT3 was increased in all tissues, showing that IL-6 signalling was activated. IL-6 mRNA tended to increase, while GLUT4, peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and adiponectin gene expression were unchanged. CONCLUSIONS/INTERPRETATION: Infusion of IL-6 for 120 min in rats during euglycaemic-hyperinsulinaemic conditions did not alter the effect of insulin on whole-body glucose homeostasis, plasma adiponectin levels or insulin signalling in target tissues. Thus, the acute effects of IL-6, associated with SOCS-3 induction, do not lead to whole-body insulin resistance. These data further underscore the importance of the chronic, and potentially tissue-specific effects of IL-6 on insulin signalling and action.
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